Compositions and methods for protecting against airborne pathogens and irritants

This application is a continuation claiming the benefit of and priority to U.S. application Ser. No. 15/691,648, filed Aug. 30, 2017, which is a continuation-in-part of U.S. application Ser. No. 15/442,604 filed Feb. 24, 2017, which claims priority to and the benefit of under 35 U.S.C. § 119(e) to provisional application Ser. No. 62/299,755, filed Feb. 25, 2016, the entire contents of each application are hereby incorporated by reference in their entirety.

The disclosure relates to compositions and methods of augmenting the health and filtering capabilities of upper respiratory epithelial and mucous membranes. In particular, the disclosure relates to compositions and methods for protecting the epithelial and mucous membranes of a subject from infection by airborne pathogens, such as viruses, bacteria, and fungi, and irritation from undesirable airborne particles such as allergens, irritants, or odorants. The disclosure further relates to compositions for application to the respiratory tract (e.g., the nasal and oral mucosa, etc.) of a human for prophylaxis of microbial and viral infections, particularly human rhinovirus (HRV) and human influenza virus infections.

Respiratory infections typically occur when airborne pathogens come into contact with mucous membranes (e.g., nasal membranes, nasal hairs, esophageal membranes, etc.) via inhaled or ingested liquid or aerosol droplets. Inhalation or ingestion of pathogens through the nose or mouth is a primary cause of respiratory disease and may also cause systemic disease such as poliomyelitis or foot and mouth disease. Airborne pathogens may enter the lungs after inhalation or ingestion, or they may bind receptors found on nasal and other membranes throughout the upper and lower respiratory tracts which serve as an entry points by which pathogens, allergens, or irritants can enter into the bloodstream and cause respiratory, as well as other, types of infection or allergic reaction. Unfortunately, there is no convenient, effective way to minimize or prevent infection or allergy by inhaled or ingested microorganisms. Therefore, there is an urgent need to develop new compositions and methods to protect against airborne pathogens, allergens, and irritants, and particularly against viruses, particularly human rhinovirus (HRV), human influenza virus, or both.

In accordance with the foregoing objectives and others, the present disclosure features compositions, such as nasal sprays, oral sprays, oral rinses, lozenges, and the like, and associated methods of using such compositions for enhancing the ability of the epithelial membranes to filter certain airborne pathogens. In particular, the disclosure provides antimicrobial compositions that prevent and treat respiratory infections and allergies caused by irritants, allergens, bacteria, fungi, and viruses. In preferred implementations, the compositions protect a subject from viral infections, particularly from human rhinovirus and/or human influenza virus.

In one aspect of the invention, a composition is provided for prophylaxis or treatment of a human subject suffering from, or at risk of suffering from, a respiratory infection. The composition may comprise one or more antimicrobial or antiviral compounds dispersed in a carrier, typically, but not necessarily, a liquid carrier. The liquid carrier is ideally, but not necessarily, of suitable rheology to be sprayed as an aerosol or fine mist. The composition may comprise one or more ingredients selected from the group consisting of an emollient, an occlusive, a humectant, a carrier, an excipient, an emulsifier, and an essential oil. In some embodiments, the composition for prophylaxis or treatment of respiratory infection may comprise active ingredient that combat infection against viruses that bind intercellular adhesion molecule 1 (ICAM-1) and/or viruses that bind sialic acid (or extracellular portions thereof). In some embodiments, the pharmaceutical composition for preventing or treating respiratory infection may comprise a pharmaceutically acceptable carrier and at least two (e.g., two, three, four) active (e.g., antimicrobial and/or antiviral, etc.) agents selected from lactoferrin (e.g., apolactoferrin, etc.), lysozyme, ICAM-1 (e.g., soluble ICAM-1, etc.), sialic acid (e.g., sialyllactose, etc.), and a neuraminidase inhibitor (e.g., quercetin, etc.). In one implementation, a composition is provided for prophylaxis or treatment of a human subject suffering from, or at risk of suffering from, infection of the respiratory tract with human rhinovirus (HRV) comprising, in a suitable liquid carrier: (i) soluble ICAM-1 (“sICAM-1”) and/or an ICAM-1 inhibitor; (ii) lysozyme; and (iii) lactoferrin (e.g., apolactoferrin, etc.). In another implementation, a composition is provided for prophylaxis or treatment of a human subject suffering from, or at risk of suffering from, infection of the respiratory tract with human influenza virus comprising, in a suitable liquid carrier: (i) sialic acid (e.g., sialyllactose, etc.); (ii) lysozyme; (iii) lactoferrin; and (iv) optionally, a neuraminidase inhibitor such as, for example, quercetin. In yet another implementation, a composition is provided for prophylaxis or treatment of a human subject suffering from, or at risk of suffering from, infection of the respiratory tract with human rhinovirus (HRV) and human influenza virus comprising, in a suitable liquid carrier: (i) soluble ICAM-1 (sICAM-1) and/or an ICAM-1 inhibitor; (ii) lysozyme; (iii) lactoferrin, (iv) sialic acid and/or a derivate therefore (e.g., sialyllactose, etc.); and (v) optionally, a neuraminidase inhibitor. Any of the compositions according to these embodiments, may further comprise one or more of zinc peroxide, copper, and silver. Any of the compositions according to these embodiments, may further comprise carrageenan. Any of the compositions according to these embodiments, may further comprise one or more of IgA, IgG, and IgM. The compositions may further comprise one or more ingredients selected from the group consisting of marshmallow extract, Calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract,extract, arrowroot extract, neem oil, vitamin C, vitamin E, and grapefruit seed extract. The carrier may be aqueous, and may include one or more pharmaceutically acceptable excipients, including, without limitation, diluents, buffering agents, pH adjusters (e.g., citric acid, etc.), thickeners and suspending agents (e.g., gum acacia, xanthan gum, hydroxypropylmethylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, etc.), rheology modifiers, preservatives (e.g., phenethyl alcohol, benzalkonium chloride, sodium EDTA, etc.), isotonicity adjusters (e.g., sodium chloride, polyols, sucrose, etc.), humectants (e.g., glycerin, etc.), surfactants (e.g., polysorbates, such as polysorbate 80, sucrose palmitate, glyceryl stearate, glyceryl stearate citrate, acetylated hydrogenated vegetable glyceride, etc.), and taste modifiers, to name a few. Any excipients should be compatible with the human mucosa and epithelium, and should not cause excessive drying or irritation to the mucosa or epithelium. The excipients should also account for the fact that water will tend to evaporate at body temperature and as such a secondary solvent may be included to aid in maintaining the soluble components in solution. The carrier may include a polyol, such as a C-Cpolyol, including without limitation, glycerin, propylene glycol, 1,3-propane diol, butylene glycol, 1,4-butane diol, erythritol, threitol, arabitol, xylitol, mannitol, sorbitol, pentylene glycol, hexylene glycol, caprylyl glycol, hydrogenated starch hydrolysates, isomalt, maltitol, and the like. The compositions may comprise an amount of an alcohol, such as ethanol, provided it is in an amount that does not irritate or dry the mucosa. In some embodiments, the compositions are free of ethanol. In one embodiment, the carrier is an aqueous carrier including from about 1-95% or from about 5-50% or from about 10-40% or from about 15-35% or from about 20-30% 1,3-propanediol, on a (v/v), (w/v), or (w/w) basis. In some embodiments, the composition may have a kinematic viscosity ranging from about 1-1,500 or from about 5-1,000 or from about 10-750 or from about 20-500 centiStokes (mm/s). The compositions may have a Newtonian or non-Newtonian rheology. The compositions may be, for example, shear thinning and/or thixotropic, such that they readily flow through a spray nozzle and form a mist of suitable droplet size on shearing, but thicken in situ to form a film on the mucosa which is resistant to clearance from the nasal or oral cavity such that the active remain on the mucosa for a time sufficient to neutralize pathogens in contact with the mucosa. Typically, the composition will be of suitable viscosity to possess a residence time on the mucosa of the nasal or oral cavities of at least 1 minute, more preferably, at least 5, 10, 15, 20, 25, or 30 minutes following application. The composition should be semi-permeable in order to permit virions and other pathogens to penetrate the film and come into contact with the active ingredients, while possessing a sufficient barrier function to inhibit evaporation of water and volatile solvents in order to maintain the actives in solution.

The pharmaceutical composition may comprise lactoferrin and soluble ICAM-1. In some embodiments, lactoferrin and soluble ICAM-1 are the sole active agents. The lactoferrin (e.g., apolactoferrin, etc.) may be present in an amount of from about from about 0.5-5000 μg/mL and the soluble ICAM-1 may be present in an amount of from about 0.01-2000 μg/mL. In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol, etc.). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of rhinovirus.

The pharmaceutical composition may comprise lysozyme and soluble ICAM-1. In some embodiments, lysozyme and soluble ICAM-1 are the sole active agents. The lysozyme may be present in an amount of from about from about 0.5-5000 μg/mL and the soluble ICAM-1 may be present in an amount of from about 0.25-20000 μg/mL. In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol, etc.). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of rhinovirus.

The pharmaceutical composition may comprise lactoferrin (e.g., apolactoferrin, etc.), lysozyme and soluble ICAM-1. In some embodiments, lactoferrin, lysozyme and soluble ICAM-1 are the sole active agents. The lactoferrin (e.g., apolactoferrin, etc.) may be present in an amount of from about from about 0.5-5000 μg/mL, the lysozyme may be present in an amount of from about from about 0.5-5000 μg/mL and the soluble ICAM-1 may be present in an amount of from about 0.25-20000 μg/mL. In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol, etc.). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of rhinovirus.

The pharmaceutical composition may comprise lactoferrin (e.g., apolactoferrin, etc.) and lysozyme. In some embodiments, lysozyme and lactoferrin are the sole active agents. The lactoferrin (e.g., apolactoferrin, etc.) may be present in an amount of from about from about 0.5-5000 μg/mL and the lysozyme may be present in an amount of from about from about 0.5-5000 μg/mL. In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of influenza.

The pharmaceutical composition may comprise lactoferrin (e.g., apolactoferrin, etc.) and sialic acid. In some embodiments, lysozyme and lactoferrin are the sole active agents. The lactoferrin (e.g., apolactoferrin, etc.) may be present in an amount of from about from about 0.5-5000 μg/mL and the sialic acid may be present in an amount of from about 0.01-2000 μg/mL (or from about 0.1-1000 μg/mL or from about 0.5-750 μg/mL) of sialic acid (e.g., sialyllactose, 6′-sialyllactose, 3-sialyllactose, 6′-sialyllactose and 3′-sialyllactose, etc.). In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol, etc.). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of influenza.

The pharmaceutical composition may comprise lactoferrin (e.g., apolactoferrin, etc.), lysozyme, and sialic acid. In some embodiments, lysozyme and lactoferrin are the sole active agents. The lactoferrin (e.g., apolactoferrin, etc.) may be present in an amount of from about from about 0.5-5000 μg/mL, the lysozyme may be present in an amount of from about from about 0.5-5000 μg/mL, and the sialic acid may be present in an amount of from about 0.01-2000 μg/mL (or from about 0.1-1000 μg/mL or from about 0.5-750 μg/mL) of sialic acid (e.g., sialyllactose, 6′-sialyllactose, 3-sialyllactose, 6′-sialyllactose and 3′-sialyllactose, etc.). In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol, etc.). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of influenza.

The pharmaceutical composition may comprise lactoferrin (e.g., apolactoferrin, etc.), lysozyme, a neuraminidase inhibitor (e.g., quercetin and isoforms thereof, isoquercetin, etc.), and sialic acid. In some embodiments, lysozyme, neuraminidase inhibitor, and lactoferrin are the sole active agents. The lactoferrin (e.g., apolactoferrin, etc.) may be present in an amount of from about from about 0.5-5000 μg/mL, the lysozyme may be present in an amount of from about from about 0.5-5000 μg/mL, the neuraminidase inhibitor may be present in an amount of from about 0.1-20 μM (or from 0.1-20 μM or from about 0.1-5 μM or from about 0.2-3 μM) neuraminidase inhibitor, and the sialic acid may be present in an amount of from about 0.01-2000 μg/mL (or from about 0.1-1000 μg/mL or from about 0.5-750 μg/mL) of sialic acid (e.g., sialyllactose, 6′-sialyllactose, 3-sialyllactose, 6′-sialyllactose and 3′-sialyllactose, etc.). In some embodiments, the lactoferrin and sialic acid and lysozyme are present in an amount such that the cytotoxicity of a mucous membrane affected by influenza (e.g., as measured by LDH release, etc.) is not increased when the composition is applied to the mucous membrane. In some embodiments, the pharmaceutical composition decreases the cytotoxicity of a mucous membrane to which the pharmaceutical composition is applied, as compared to an otherwise identical composition not comprising sialic acid and/or lactoferrin and/or lysozyme. In preferred embodiments, the pharmaceutical composition comprises a carrier that is from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol (e.g., 1,3-propandiol, etc.). In some embodiments, the pharmaceutical composition may be used for the treatment or prophylaxis of a respiratory disease. In preferred embodiments, the composition may be used for the treatment of influenza. Typically the neuraminidase inhibitor is isoquercetin.

In some embodiments, the composition may comprise:

In some embodiments, the composition may comprise:

In some embodiments, the composition may comprise:

The pharmaceutical composition may be used in a method of preventing or treating respiratory infection. The respiratory infection may be due to human rhinovirus and/or human influenza virus. In some embodiments, a composition for preventing or treating respiratory infection from human rhinovirus (HRV) may comprise:

(i) about 0.00000001% to about 10% by weight soluble ICAM-1;

(ii) about 0.000005% to about 10% by weight lysozyme; and

(iii) about 0.00000025% to about 10% by weight lactoferrin;

and a pharmaceutically acceptable carrier and, optionally, one or more excipients.

In some embodiments, a composition for preventing or treating respiratory infection from human rhinovirus (HRV) may comprise:

(i) about 0.000001%-1% (or to about 0.1%) by weight soluble ICAM-1;

(ii) about 0.0001% to about 5% (or to about 1%) by weight lysozyme; and

(iii) about 0.00005% to about 5% (or to about 0.5%) by weight lactoferrin;

and a pharmaceutically acceptable carrier and, optionally, one or more excipients.

In some embodiments, a composition for preventing or treating respiratory infection from human rhinovirus (HRV) may comprise:

(i) about 0.0005%-0.05% by weight soluble ICAM-1; and/or

(ii) about 0.0025% to about 0.25% by weight lysozyme; and/or

(iii) about 0.00005% to about 0.1% by weight lactoferrin;

and a pharmaceutically acceptable carrier and, optionally, one or more excipients.

In some embodiments, a composition for preventing or treating respiratory infection from human influenza virus may comprise:

In some embodiments, a composition for preventing or treating respiratory infection from human influenza virus may comprise:

In some embodiments, a composition for preventing or treating respiratory infection from human influenza virus may comprise:

In some embodiments, the compositions of the invention will be aqueous solutions or suspensions comprising from about 0.5-5000 μg/mL (or from about 1-1000 μg/mL or from about 5-500 μg/mL) of lactoferrin (e.g., apolactoferrin, etc.). In some embodiments, the compositions of the invention will be aqueous solutions or suspensions comprising from about 0.25-20000 μg/mL (or from about 0.25-10000 μg/mL or from about 1-5000 μg/mL or from about 25-2500 μg/mL or from about 1000-12000 μg/mL) of lysozyme. In some embodiments, the compositions of the invention will be aqueous solutions or suspensions comprising from about 0.01-2000 μg/mL (or about 0.01-1000 μg/mL or from about 0.1-600 μg/mL or from about 0.1-100 μg/mL or from about 0.5-50 μg/mL) of ICAM-1 (e.g., soluble ICAM-1, etc.). In some embodiments, the compositions of the invention will be aqueous solutions or suspensions comprising from about 0.01-2000 μg/mL (or from about 0.1-1000 μg/mL or from about 0.5-750 μg/mL) of sialic acid (e.g., sialyllactose, etc.). In some embodiments the composition comprises a concentration of 6′-sialylllactose of about 0.01-2000 μg/mL (or from about 0.1-1000 μg/mL or from about 0.5-750 μg/mL) and a concentration of 3′-sialyllactose of about 0.01-2000 μg/mL (or from about 0.1-1000 μg/mL or from about 0.5-750 μg/mL). In some embodiments, the compositions of the invention will be aqueous solutions or suspensions comprising from about 0.005-1000 μg/mL (or from about 0.5-500 μg/mL or from about 0.25-375 μg/mL) of 3′ sialyllactose and/or from about 0.005-1000 μg/mL (or from about 0.5-500 μg/mL or from about 0.25-375 μg/mL) of 6′ sialyllactose. In some embodiments, the compositions will comprise from about 0.1-20 μM (or from 0.1-20 μM or from about 0.1-5 μM or from about 0.2-3 μM) neuraminidase inhibitor. In some embodiments, the compositions will comprise from about 0.1-20 μM (or from 0.1-20 μM or from about 0.1-5 μM or from about 0.2-3 μM) quercetin.

The pharmaceutical compositions according to the invention may be in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge. The carrier of the pharmaceutical composition may be selected to provide residence time of the composition on the nasal and/or oral mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes following application. In some embodiments, the composition for application to the nasal or oral mucosa comprises one or more antiviral and/or antimicrobial agents dispersed in a liquid carrier comprising from about 1-99% (v/v) water or from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol. In some embodiments, the pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) 1,3-propanediol. The composition may be capable of being sprayed or ingested onto the mucosa, and is adapted to remain on the mucosa for at least 5 minutes (or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes) following application without substantially irritating or drying the mucosa.

Methods for prophylaxis and/or treatment of various viral infections are provided. In some embodiments, the method for prophylaxis and/or treatment of human rhinovirus infection, comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has human rhinovirus in contact therewith.

In one aspect, the invention provides for a pharmaceutical composition for preventing or treating subjects suffering from or at risk of suffering from a respiratory infection comprising: one or more antimicrobial or antiviral compounds; and a base mixture comprising one or more ingredients selected from the group consisting of a carrier, an emollient, an occlusive, a humectant, a polyol, an emulsifier, a preservative, a thickener or suspending agent, a surfactant, a pH adjuster, an isotonicity agent, and an essential oil. In an embodiment, the antimicrobial or antiviral compound is one or more selected from the group consisting of an antibody such as IgA, IgG, or IgM, a soluble ICAM-1, an ICAM-1 inhibitor, sialic acid, a neuraminidase inhibitor, lactoferrin, a lysozyme, zinc, zinc compounds, silver, silver compounds, copper, copper compounds, and combinations thereof. In an embodiment, the neuraminidase inhibitor is selected from the group consisting of quercetin, oseltamivir, zanamivir, laninamivir, and peramivir. In an embodiment, the ICAM-1 inhibitor is selected from the group consisting of an anti-ICAM-1 antibody, cytokine, CD11a, ezrin (EZR), CD18, glycyrrhetinic acid, pyrrolidinedithiocarbamate, NFkB activation inhibitor, heterocyclic thiazole, lipoic acid, efalizumab, 4-[(4-Methylphenyl)thio]thieno[2,3-c]pyridine-2-carboxamide, silibinin, stilbenes, (+)-epigalloyl-catechin-gallate [(+)-EGCG], and combinations thereof. In an embodiment, the one or more antimicrobial or antiviral compounds include soluble ICAM-1 and sialic acid (e.g., sialyllactose, 3′ sialyllactose, and/or 6′ sialyllactose, etc.). In an embodiment, the one or more antimicrobial or antiviral compounds include lactoferrin, lysozyme, neuraminidase inhibitor, IgA, IgG, IgM, zinc peroxide (ZnO), copper, and silver. In an embodiment, the respiratory infection is selected from the group consisting of a rhinovirus infection, an influenza virus infection, a fungal infection, and a bacterial infection. In an embodiment, one or more ingredients are selected from the group consisting of a marshmallow extract, a calendula extract, a citrus peel extract, a honey extracts, a rosemary extracts, a myrhh extract, aextract, a arrowroot extract, a neem oil, an argan oil, a vitamin C, a vitamin E, a grapefruit seed extract, and combinations thereof.

In one aspect, the invention provides for a method of prophylaxis or treatment of respiratory infection in subjects suffering from or at risk of suffering from respiratory infection comprising: determining a subject is suffering from or at risk of suffering from a respiratory infection; and administering a composition according to the invention comprising one or more antimicrobial or antiviral compounds and a base mixture comprising one or more ingredients selected from the group consisting of a carrier, an emollient, an occlusive, a humectant, an emulsifier, and an essential oil. In an embodiment, the one or more antimicrobial or antiviral compounds comprise soluble ICAM-1. In an embodiment, the one or more antimicrobial or antiviral compounds comprise sialic acid or a derivative thereof (e.g., sialyllactose, etc.). In one embodiment, the one or more antimicrobial or antiviral compounds comprise lactoferrin (e.g., apolactoferrin, etc.). In one embodiment, the one or more antimicrobial or antiviral compounds comprise lysozyme. In one embodiment, the one or more antimicrobial or antiviral compounds comprise a neuraminidase inhibitor. In one embodiment, the one or more antimicrobial or antiviral compounds comprise IgA, IgG, and/or IgM. In one embodiment, the one or more antimicrobial or antiviral compounds comprise zinc peroxide (ZnO), copper, and/or silver. The compositions may be administered by any suitable route, including orally, topically, nasally, and combinations thereof. In an embodiment, the composition is administered to nasal membranes. In an embodiment, the composition is administered using a device selected from the group consisting of an atomizer, an inhaler, a nebulizer, a spray bottle, and a spray pump. The composition may include a propellant or may be free of propellants.

These and other aspects of the invention will be better understood by reference to the following Detailed Description and appended claims.

The present disclosure may be understood more readily by reference to the following detailed description and the Examples included therein. Before the present methods and techniques are disclosed and described, it is to be understood by one of skill in the art that this disclosure is not to be limited to the specific analytical or synthetic methods described herein. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this disclosure belongs.

By “agent” or “therapeutic agent” is meant any small molecule chemical compound, antibody, nucleic acid molecule, or polypeptide or fragments thereof. By “therapeutic agent” is meant any of the compositions dedicated to preventing or treating respiratory infections described herein.

By “ameliorate” is meant decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a respiratory disease or a symptom thereof.

By “analog” is meant a molecule that is not identical, but has analogous functional or structural features. For example, a polypeptide analog retains the biological activity of a corresponding naturally-occurring polypeptide, while having certain biochemical modifications that enhance the analog's function relative to a naturally occurring polypeptide. Such biochemical modifications could increase the analog's protease resistance, membrane permeability, or half-life, without altering, for example, ligand binding. An analog may include an unnatural amino acid.

As used herein “an interfering RNA” refers to any double stranded or single stranded RNA sequence, capable—either directly or indirectly (i.e., upon conversion)—of inhibiting or down regulating gene expression by mediating RNA interference. Interfering RNA includes, but is not limited to, small interfering RNA (“siRNA”) and small hairpin RNA (“shRNA”). “RNA interference” refers to the selective degradation of a sequence-compatible messenger RNA transcript.

As used herein “an shRNA” (small hairpin RNA) refers to an RNA molecule comprising an antisense region, a loop portion and a sense region, wherein the sense region has complementary nucleotides that base pair with the antisense region to form a duplex stem. Following post-transcriptional processing, the small hairpin RNA is converted into a small interfering RNA by a cleavage event mediated by the enzyme Dicer, which is a member of the RNase III family.

As used herein “an RNAi” (RNA interference) refers to a post-transcriptional silencing mechanism initiated by small double-stranded RNA molecules that suppress expression of genes with sequence homology.

As used herein, “changed as compared to a control” sample or subject is understood as having a level of the analytic or diagnostic or therapeutic indicator to be detected at a level that is statistically different than a sample from a normal, untreated, or control sample or subject. Control samples include, for example, cells in culture, one or more laboratory test animals, or one or more human subjects. Methods to select and test control samples are within the ability of those skilled in the art. An analytic substance can be a naturally occurring substance that is characteristically expressed or produced by the cell or organism (e.g., antibodies, pathogenic peptides or particles, and the like) or a substance produced by a reporter construct (e.g., β-galactosidase or luciferase, etc.). Depending on the detection method used, the amount and measurement of the change may vary. Determination of statistical significance is within the ability of those skilled in the art.

As used herein, the term “co-administering,” or “co-administration,” and the like refers to the act of administering two or more agents (e.g., an antimicrobial agent and an anti-viral agent, etc.), compounds, therapies, or the like, at or about the same time. The order or sequence of administering the different agents of the disclosure, e.g., antibiotics, antivirals, antifungals, or immunotherapeutic agents, may vary and is not confined to any particular sequence. Co-administering may also refer to the situation where two or more agents are administered to different regions of the body or via different delivery schemes, e.g., where a first agent is administered intranasally and a second agent is administered systemically, or vice versa. Co-administering may also refer to two or more agents administered via the same delivery scheme, e.g., where a first agent is administered intranasally and a second agent is administered intranasally.

As used herein, the terms “comprises,” “comprising,” “containing” and “having” and the like are open-ended as defined by U.S. Patent law and can mean “includes,” “including,” and the like. The terms “consisting essentially of” or “consists essentially” likewise have the meaning ascribed to them in U.S. Patent law and are open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited are not changed by the presence of more than that which is recited, but excludes prior art embodiments.

“Contacting a cell” is understood herein as providing an agent to a cell (e.g. a nasal membrane cell, etc.), such that the agent may interact with the cell (e.g., nasal membrane cell to be treated, etc.) and/or taken up by the cell, and have an effect on the cell. The agent (e.g., an antimicrobial or antiviral agent, etc.) may be delivered to the cell directly (e.g., by addition of the agent to a gel or aerosol formulation for nasal delivery, etc.). One of ordinary skill in the art will readily understand that administration of a therapeutic agent to a subject involves contacting the therapeutic agent with a cell or tissue of the subject.